A number of additional questions regarding prophylaxis and treatment of MAC disease remain. Should MAC prophylaxis be stopped for patients whose CD4 counts increase above the threshold of risk after treatment with highly active antiretroviral therapy? Are the CD4 cells recovered in the latter situation functional with regard to the immune response to MAC infection? How will the incidence and epidemiology of MAC disease change with the advent of highly effective antiretroviral therapy? Once disease occurs, what proportion of patients treated with a macrolide-containing regimen will ultimately fail or relapse on therapy and what factors determine this? Are there regimens that will significantly reduce the risk of failure or relapse due to drug resistance? How should patients who fail or relapse on initial therapy be treated? How can the drugs available for prophylaxis and treatment be most effectively used in the context of protease inhibitor-based antiretroviral therapy or other drug therapies with which antimycobacterial agents may interact? Future directions in research related to MAC disease will require us to address not only these questions but also to develop new drugs with increased activity against this organism.
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